Metabolic state has a profound impact on cognitive function and our perception of the external world. However, the mechanisms underlying behavioral changes during the transition from mild to severe starvation are poorly understood. Here, we propose to take advantage of the anatomical simplicity and genetic tractability of Drosophila to study how shifts in metabolic state shape olfactory circuit function and thus impact appetitive olfactory behavior. There are remarkable similarities between Drosophila and mammals in the organization and molecular regulation of olfactory systems, suggesting shared principles in the neurobiology of hunger. Elucidating how changes in olfactory neural circuits impact the perception of food quality and dietary selections may lead to a better understanding of factors that contribute to obesity as well as anorexia in the infirm and elderly. The experiments outlined here investigate the hypotheses that the decline of insulin, a global satiety signal, triggers local neuropeptide signaling to recruit distinct neuronal populations at different stages of starvation. The goals of these experiments are: 1) investigating the temporal expression pattern of sNPF receptors in different neuronal populations; 2) investigating the role of local sNPF (a homolog of NPY in Drosophila) signaling in modulating neuronal excitability in a higher order olfactory center; 3) Investigate changes across the broader gamma lobe MBON network.

Public Health Relevance

Obesity is a seemingly unstoppable epidemic that affects a large population. The work of this proposal is basic science that seeks to reveal the connection between olfaction and appetitive behavior. Defining the olfactory circuits that modulate feeding behavior will create a knowledge base from which potential molecular targets can be evaluated for future therapeutic interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK092640-06
Application #
9319001
Study Section
Molecular Neurogenetics Study Section (MNG)
Program Officer
Hyde, James F
Project Start
2011-07-26
Project End
2021-02-28
Budget Start
2017-03-01
Budget End
2018-02-28
Support Year
6
Fiscal Year
2017
Total Cost
$387,500
Indirect Cost
$137,500
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Tao, Xiaodong; Lin, Hui-Hao; Lam, Tuwin et al. (2017) Transcutical imaging with cellular and subcellular resolution. Biomed Opt Express 8:1277-1289
Sethi, Sachin; Wang, Jing W (2017) A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster. Elife 6:
Kim, Susy M; Su, Chih-Ying; Wang, Jing W (2017) Neuromodulation of Innate Behaviors in Drosophila. Annu Rev Neurosci 40:327-348
Kim, Susy M; Wang, Jing W (2016) Hygrosensation: Feeling Wet and Cold. Curr Biol 26:R408-10
Ko, Kang I; Root, Cory M; Lindsay, Scott A et al. (2015) Starvation promotes concerted modulation of appetitive olfactory behavior via parallel neuromodulatory circuits. Elife 4:
Su, Chih-Ying; Wang, Jing W (2014) Modulation of neural circuits: how stimulus context shapes innate behavior in Drosophila. Curr Opin Neurobiol 29:9-16
Sen, Sonia; Cao, Deshou; Choudhary, Ramveer et al. (2014) Genetic transformation of structural and functional circuitry rewires the Drosophila brain. Elife 3:
Chihara, Takahiro; Kitabayashi, Aki; Morimoto, Michie et al. (2014) Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila. PLoS Genet 10:e1004437
Zaninovich, Orel A; Kim, Susy M; Root, Cory R et al. (2013) A single-fly assay for foraging behavior in Drosophila. J Vis Exp :e50801
Kim, Susy M; Wang, Jing W (2013) Calcium imaging of pheromone responses in the insect antennal lobe. Methods Mol Biol 1068:179-87

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